This application provides funds for the Washington University Drug Abuse Research Center. The Center consists of four units: core; Project 1, Narcotics and the Hypothalamic-Pituitary-Gonadal Axis; Project 3, A Neuroanatomical Approach to Drug Addiction; and Project 2, Narcotic Effects on the Hypothalamus: Localization Studies. The core support budget contains funds for the overall administration and integration of the Center's research and training activities. In addition, funds are available to bring speakers to the Center to present their drug-related research. The overall goal of Project 1 is to understand the mechanisms underlying the disruptive effects of the narcotics on the hypothalamic-pituitary-gonadal axis in the male rat. Specifically, our studies are directed to an examination of the effects of chronic narcotic administration and acute drug treatment on luteinizing hormone, testosterone, and the structural and functional integrity of the secondary sex organs in the male rat and human. The goal of Project 3 is to more fully examine the neural pathways connecting the hypothalamus to the rest of brain. Since narcotics directly alter hypothalamic function a full understanding of the mechanisms underlying these effects will only be achieved by knowing completely the organization of the neural input and projects to the hypothalamus. The specific aims of Project 2 are to define the neuroanatomical locus of action of the narcotics within the hypothalamus. These studies include a detailed pharmacological, biochemical, and neuroanatomical investigation of the whorls of the endoplasmic reticulum observed in the arcuate nucleus of morphine-treated animals. A further goal is to attempt to determine at a microregional level in brain, the effects of the narcotics on the hypothalamic releasing factors of several anterior pituitary hormones. The Center represents a broadly based, interdisciplinary effort to understand the basic cellular biochemical adaptations which occur as a consequence of acute and chronic narcotic administration.